Abstract

BackgroundCaloric restriction (CR) can help in improving heart function. There is as yet no consensus on the mechanism of the effect of CR. Silent mating-type information regulation 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), and mTOR are key players in metabolic stress management. We aimed to explore the effect of CR on the myocardial SIRT1/AMPK/mTOR pathway in mice.MethodsThirty-six 6-week-old male C57BL/6J mice were randomly divided into three groups: normal control group (NC group, n = 12), high-energy group (HE group, n = 12) and CR group (n = 12) according to different diets. After 11 months, western blot was used to examine proteins such as p-AMPK, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), SIRT1, and p-mTOR, whereas real-time PCR was used to examine the expression of AMPK, PGC-1α, and SIRT1 transcripts.ResultsCompared to the HE group, the CR group displayed increased expression of myocardial p-AMPK protein, SIRT1 protein and mRNA, and PGC-1a mRNA. However, no difference was observed in the expression of p-mTOR protein and mTOR mRNA in the myocardium among the three groups.ConclusionsCR improves the SIRT1/AMPK/PGC-1α pathway in mice myocardium with no effect on the mTOR pathway.

Highlights

  • Caloric restriction (CR) can help in improving heart function

  • The results revealed that both protein and transcript levels of myocardial Silent mating-type information regulation 1 (SIRT1) were elevated in the CR group compared to the HE group (Figs. 1c and 2c), suggesting that CR activates SIRT1 to exert its cardiovascular protective effect

  • The transcript levels of SIRT1 and PGC-1α showed an increase but there was no significant difference in the protein and mRNA levels of p-mTOR between the three groups, suggesting that the role of CR in cardiovascular function may be mainly mediated through the SIRT1/AMPK pathway

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Summary

Introduction

Caloric restriction (CR) can help in improving heart function. There is as yet no consensus on the mechanism of the effect of CR. Silent mating-type information regulation 1 (SIRT1), adenosine ­monophosphate-activated protein kinase (AMPK), and mTOR are key players in metabolic stress ­management. We aimed to explore the effect of CR on the myocardial SIRT1/AMPK/mTOR pathway in mice. After 11 months, western blot was used to examine proteins such as p-AMPK, peroxisome proliferator-­ activated receptor gamma coactivator 1-alpha (PGC-1α), SIRT1, and p-mTOR, whereas real-time PCR was used to examine the expression of AMPK, PGC-1α, and SIRT1 transcripts. Results: Compared to the HE group, the CR group displayed increased expression of myocardial p-AMPK protein, SIRT1 protein and mRNA, and PGC-1a mRNA. No difference was observed in the expression of p-mTOR protein and mTOR mRNA in the myocardium among the three groups. Conclusions: CR improves the SIRT1/AMPK/PGC-1α pathway in mice myocardium with no effect on the mTOR pathway

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